Olfaction, the sense of smell, contributes significantly to quality of life and overall human health. Volatile chemicals in the environment are detected by a large family of odorant receptors, the largest repertoire of genes in the mammalian genome. The odorant receptor family comprises three phylogenetically distinct types of receptors: Class I and Class II receptors (comprising over 1000 genes), and a recently discovered family of Trace Amine-Associated Receptors or TAARs (14 genes). This small gene family is well-conserved in many mammalian species including humans, suggesting that TAARs have a unique and important role in odor perception. It has been speculated that the TAARs respond to volatile social cues. However, the functional properties of these receptors are poorly characterized. The goal of this proposal is to define the functional properties of TAARs in the intact mammalian olfactory system in order to test the hypothesis that these receptors respond specifically or preferentially to a subset of odorants (i.e. amines). I will generate several strains of gene-targeted mice in which the olfactory sensory neurons expressing defined TAAR genes and their associated glomeruli in the olfactory bulb are fluorescently labeled. I will then characterize the response profiles of the receptors by imaging odor-evoked activity from the genetically defined glomeruli. The proposed experiments will characterize for the first time the function of mammalian TAARs in vivo, and will serve as the first step in determining how these receptors contribute odor perception in mammals. PUBLIC HEALTH RELEVANCE: The sense of smell is critical for quality of life and overall human health. We are taking a novel approach to characterize how odorants are detected under normal conditions by a newly discovered class of olfactory receptors, the trace amine associated receptors. Our methods will allow us to characterize for the first time how molecular interactions at these receptors contribute to mammalian odor perception.